In order to maximize the potential benefit of research using newborn screening residual dried blood samples (DBS), a paradigm shift will be necessary to develop an infrastructure in which parental consent is obtained and the results of genomics research using these samples will be returned to the parents of individual research participants. The goal of this project is to facilitate the development of the normative and legal framework necessary to return results to individual participants in this context. This goal is consistent with the new vision of the National Human Genome Research Institute which discusses the need to re-examine the framework for oversight of genomics research involving human subjects. A systems-based approach will be used to consider the processes involved in using DBS for research and how results might be returned to the parents of individual research participants. Particular attention will be paid to the normative and legal obligations of each stakeholder involved in these processes and to elements that may be unique to newborn screening. These stakeholders include state departments of health, biorepository managers, researchers, and clinicians. A multi-disciplinary team with expertise in law, bioethics, medical genetics, and clinical care will conduct the research. The Specific Aims of the proposed research are as follows: SPECIFIC AIM 1: To evaluate lessons learned regarding the development of state policies in the context of historical experience with the expansion of newborn screening and the development of biorepositories using DBS. SPECFIC AIM 2: To identify key gaps in the regulatory framework in which legal considerations related to the return of results of genomics research using DBS have not been fully considered. SPECIFIC AIM 3: To develop specific recommendations regarding key elements that need to be addressed by state policy makers in order to implement a system in which results from genomics research with DBS are returned to individual participants. PUBLIC HEALTH RELEVANCE: In order to maximize the potential benefit of research using newborn screening residual dried blood samples (DBS), a paradigm shift will be necessary to develop an infrastructure in which parental consent is obtained and the results of genomics research using these samples will be returned to the parents of individual research participants. The goal of this project is to facilitate the development of the ethical and legal framework necessary to return results of genomics research using DBS to the parents of individual participants.